The c-myb protooncogene plays a crucial role during hematopoiesis and has been implicated in the evolution of leukemia and lymphoma, as well as tumors of the breast, colon and lung. The transforming potential of c-myb can be activated by structural modifications or inappropriate expression. However, little is known about the function of c-myb during hematopoiesis and a major impediment to understanding c-myb function has been the lack of genetic system to study hematopoiesis in the absence of c-myb activity. Mice homozygous for null mutations at the c-myb locus are embryonic lethal and have been of minimal use. The goal of this proposal is to develop a genetic system that will allow the manipulation of c-myb during hematopoiesis and will focus on the role played by c-myb during B-lymphocyte differentiation. The two specific aims are: 1) to characterize c-myb expression during normal B cell development and 2) to utilize a Cre/loxP approach to make conditional null mutations at the c-myb locus that will only affect the B cell lineage. Once the basic loxP marked c-myb mice are built they will provide a crucial reagent for understanding c-myb function in any hematopoietic or nonhematopoietic lineage of interest, understanding the contribution of c-myb structural features (including phosphorylation sites) to c-myb function and offering a system to rationally identify c-myb target promoters.